rs10879348

Variant names:

• chr12-71972859-G-A
• rs10879348
• NM_173353.4:c.805+144G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-71972859-G-A
• chr12-71972859-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.805+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 835,682 control chromosomes in the GnomAD database, including 2,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.062 (457 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1550 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 1 publications found

Genes affected

TPH2 (HGNC:20692): (tryptophan hydroxylase 2) This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173353.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	NM_173353.4	MANE Select	c.805+144G>A		intron	N/A	NP_775489.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000333850.4	TSL:1 MANE Select	c.805+144G>A		intron	N/A	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9358 AN: 151988 Hom.: 444 Cov.: 32

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0542

GnomAD4 exome AF: 0.0460 AC: 31428 AN: 683578 Hom.: 1550 AF XY: 0.0500 AC XY: 17907 AN XY: 357818

African (AFR) AF: 0.0943 AC: 1617 AN: 17146

American (AMR) AF: 0.112 AC: 2890 AN: 25904

Ashkenazi Jewish (ASJ) AF: 0.0240 AC: 394 AN: 16394

East Asian (EAS) AF: 0.100 AC: 3486 AN: 34820

South Asian (SAS) AF: 0.156 AC: 8659 AN: 55348

European-Finnish (FIN) AF: 0.0383 AC: 1295 AN: 33810

Middle Eastern (MID) AF: 0.0522 AC: 135 AN: 2588

European-Non Finnish (NFE) AF: 0.0243 AC: 11257 AN: 463172

Other (OTH) AF: 0.0493 AC: 1695 AN: 34396

GnomAD4 genome AF: 0.0618 AC: 9403 AN: 152104 Hom.: 457 Cov.: 32 AF XY: 0.0663 AC XY: 4932 AN XY: 74362

African (AFR) AF: 0.0932 AC: 3865 AN: 41478

American (AMR) AF: 0.0986 AC: 1505 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.126 AC: 649 AN: 5170

South Asian (SAS) AF: 0.167 AC: 802 AN: 4814

European-Finnish (FIN) AF: 0.0441 AC: 467 AN: 10588

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1827 AN: 68000

Other (OTH) AF: 0.0579 AC: 122 AN: 2108

Alfa AF: 0.0182 Hom.: 12

Bravo AF: 0.0643

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.24
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10879348; hg19: chr12-72366639;